Cell-based therapies for cardiovascular, lung and blood diseases offer a new paradigm for advancing and transforming patient care. Translational and early-phase clinical research has demonstrated that cell-based therapies may improve left ventricular function, reduce myocardial ischemia and lead to improved lung function. Cystic fibrosis (CF) patients have mutations in the gene encoding the chloride transport protein CFTR which when defective in the airway epithelium results in significant pulmonary morbidity and eventual mortality. The morbidities are associated with inefficient resolution of pulmonary infection with Pseudomonas aeruginosa and the ensuing inflammatory response. The question is what is responsible for this over-zealous response to bacteria burden and why can't the immune system resolve the infection efficiently. Although dysfunctional airway clearance, mucous plugging and epithelial chemokine production are major contributors to CF pulmonary disease, the inability to of the innate immune response to efficiently clear bacteria and "turn-off" the resounding inflammation is still a prominent question. Cell-based therapies as adjunct intervention may be viable options in resolving the inflammation and pulmonary injury associated with the cystic fibrosis pulmonary disease. The studies outlined in this proposal are aimed at evaluating whether bone marrow transplantation or adult human derived mesenchymal stem cells therapy has a beneficial effect on inflammatory outcomes in the course of infection with Pseudomonas aeruginosa in animals deficient in CFTR function. PUBLIC HEALTH RELEVANCE: Cystic fibrosis (CF) patients have mutations in the gene encoding the chloride transport protein CFTR which when defective in the airway epithelium results in significant pulmonary morbidity and eventual mortality. The morbidities are associated with inefficient resolution of pulmonary infection with Pseudomonas aeruginosa and the ensuing inflammatory response. The question is what is responsible for this over-zealous response to bacteria burden and why can't the immune system resolve the infection efficiently. Although dysfunctional airway clearance, mucous plugging and epithelial chemokine production are major contributors to CF pulmonary disease, the inability to of the innate immune response to efficiently clear bacteria and "turn-off" the resounding inflammation is still a prominent question. Cell-based therapies such as bone marrow transplantation and mesenchymal stem cells have the potential to be developed as alternative therapeutic strategies combating the genetic anomaly and the disease progression in cystic fibrosis through the ability to enhance the host's "self" immunity enabling efficient infection and inflammation resolution.